Carlo Ancelotti's side ran riot in the first leg in Gelsenkirchen last month, with braces from Cristiano Ronaldo, Karim Benzema and Gareth Bale helping the visitors to a 6-1 win.
That scoreline all but confirms Real's presence in the last eight of Europe's premier club competition, with Schalke unlikely to produce a rare comeback on Tuesday at the Bernabeu.
In UEFA competition, Jens Keller's men have been beaten in all three ties where they lost at home in the first leg and will need a minor miracle if they are to arrest that run against the Spanish table-toppers.
Real have scored 26 goals in the Champions League this season and remain on course for a treble due to impressive performances in La Liga and the Copa del Rey.
Ancelotti's side have won their last 16 home games in all competitions and have conceded only twice at the Bernabeu since the turn of the year.
Real maintained their three-point lead in the Spanish top flight at the weekend thanks to a 1-0 win over Malaga, sealed by Ronaldo.
While Ancelotti's side are in fine fettle domestically, Schalke have also been in impressive form themselves since returning from Germany's mid-season break.
Keller's men have lost once twice in all competitions in 2014 - the drubbing at the hands of Real and an equally comprehensive 5-1 defeat to runaway Bundesliga leaders Bayern Munich.
While they will most likely see their European campaign ended on Tuesday in Madrid, the form of Klaas-Jan Huntelaar has helped put Schalke in with a great chance of Champions League qualification for next season.
The former Real striker has eight goals in nine games since returning from a knee injury, helping them to third in the German top flight and Schalke will need him to produce on Tuesday if they are to achieve the impossible in the Spanish capital.
Captain Benedikt Howedes acknowledged the dream of European glory is over for another season but explained his team-mates will give it their all regardless.
"We want to sign off from Europe on a high note. Unfortunately, losing 6-1 to Real brought a good Champions League season to an end," he told the club's official website.
"What's more important now is that the last impression we leave in this year's competition is positive for us and the club."
Midfielder Kevin-Prince Boateng added: "We want to get stuck into things again, even if we know it's impossible to progress. We're not going to Madrid to see the sights. We want to put in a good performance."
Benzema (thigh) is a worry for Ancelotti after limping off in Saturday's win over Malaga while Jefferson Farfan may not feature for the visitors due to a knee complaint.
